Do beta-adrenergic drugs increase microcirculatory blood flow in the gut in sepsis?

Keywords

Septic ShockDobutamineRegional FlowLaser Doppler FlowmetryDopexamine

Introduction

Splanchnic blood flow is impaired in sepsis [1]. Therefore, beta-adrenergic agents are frequently administered in sepsis to increase global oxygen delivery in an attempt to increase splanchnic blood flow as well. However, changes in microcirculation can not be predicted by changes in systemic blood flow [2] and the effects of beta-adrenergic drugs on the splanchnic and gut mucosal circulation in sepsis is still not well understood. The aim of this study was to measure the effects of dopexamine and dobutamine, on systemic flow, regional flow and microcirculatory blood flow in the intestinal mucosa in septic shock.

Materials and methods

Systemic flow (CI), regional flow (superior mesenteric artery) and microcirculatory blood flow (MBF) were measured in nine sedated (midazolam & fentanyl) and ventilated pigs (20-24 kg). MBF in the mucosa of the stomach, jejunum and colon was measured with multichannel laser Doppler flowmetry. Septic shock was induced by fecal peritonitis at 0 min. After 240 min, i.v. fluids were administered to alter hypodynamic shock to hyperdynamic septic shock. At 360 min each animal received either i.v. infusion of dopexamine (1.0 µg/kg/min, increased after 30 min to 2.0 µg/kg/min for another 30 min) or dobutamine (5 µg/kg/min, increased after 30 min to 10 µg/kg/min for another 30 min) in a random order. After 30-60 min recovery period a new baseline was taken before infusion with the other test drug was started.

Results and discussion

Results are presented in the Table as percent of baseline ± SEM. Changes within each parameter were tested with ANOVA for repeated measurements. *P < 0.05; -P < 0.01; -P < 0.001. Both the tested beta-adrenergic drugs increased cardiac index significantly. However, regional blood flow was only increased with dopexamine, but not with dobutamine. Microcirculatory blood flow in the gastric mucosa was also significantly increased with dopexamine, but not with dobutamine. Neither drug appeared to influence microcirculatory flow in the intestinal mucosa.

Table

Dopexamine

Dopexamine

Dobutamine

Dobutamine

Drug dosage

1 µg/kg/min

2 µg/kg/min

5 µg/kg/min

10 µg/kg/min

Mean arterial pressure (mmHg)

70 ± 4.6

71 ± 4.3

70 ± 4.3

66 ± 3.6

Cardiac index (% of baseline)

119 ± 4.3-

135 ± 5.7-

124 ± 4.7-

148 ± 6.4-

Superior mesenteric artery flow (%)

115 ± 5.7*

119 ± 6.0-

104 ± 3.0

103 ± 4.8

MBF in the gastric mucosa (%)

105 ± 1.7

111 ± 3.3-

103 ± 2.0

101 ± 4.2

MBF in the jejunal mucosa (%)

92 ± 5.4

98 ± 5.7

105 ± 4.3

97 ± 3.2

MBF in the colonic mucosa (%)

103 ± 2.1

102 ± 2.7

101 ± 2.2

99 ± 3.9

Conclusion

Although the beta-adrenergic agents significantly increased cardiac output the mucosa of the gastrointestinal tract appeared to profit very little from increased systemic flow. Dobutamine did neither influence regional flow or microcirculatory flow. Dopexamine improved both regional and gastric mucosal flows, but had no effects on mucosal flow in the small and large bowel.